Antitumor Effects and Tumor-specificity of Guaiazulene-3-Carboxylate Derivatives Against Oral Squamous Cell Carcinoma .

Aim: The aim of this study was to investigate the antitumor potential of guaiazulene-3-carboxylate derivatives against oral malignant cells.

Materials And Methods: Twelve guaiazulene-3-carboxylate derivatives were synthesized by introduction of either with alkyl group [], alkoxy group [], hydroxyl group [] or primary amine [] at the end of sidechains. Tumor-specificity (TS) was calculated by the ratio of mean 50% cytotoxic concentration (CC) against 3 human oral mesenchymal cell lines to that against 4 human oral squamous cell carcinoma (OSCC) cell lines. Potency-selectivity expression (PSE) was calculated by dividing TS value by CCvalue against OSCC cell lines. Cell cycle analysis was performed by cell sorter.

Results: [] showed the highest TS and PSE values, and induced the accumulation of both subG and G/M cell populations in HSC-2 OSCC cells. Quantitative structure-activity relationship analysis demonstrated that their tumor-specificity was correlated with chemical descriptors that explain the 3D shape, electric state and ionization potential.

Conclusion: Alkoxyl guaiazulene-3-carboxylates [] can be potential candidates of lead compound for developing novel anticancer drugs.